Search Results (3)

A series of amphiphilic arborescent copolymers of generations G1 and G2 with an arborescent poly(γ-benzyl L-glutamate) (PBG) core and poly(ethylene oxide) (PEO) chain segments in the shell, PBG-g-PEO, were synthesized and evaluated as drug delivery nanocarriers. The PBG building blocks were generated by ring-opening polymerization of γ-benzyl L-glutamic acid N-carboxyanhydride (Glu-NCA) initiated with n-hexylamine. Partial or full deprotection of the benzyl ester groups followed by coupling with PBG chains yielded a comb-branched (arborescent polymer generation zero or G0) PBG structure. Additional cycles of deprotection and grafting provided G1 and G2 arborescent polypeptides. Side chains of poly(ethylene oxide) were then randomly grafted onto the arborescent PBG substrates to produce amphiphilic arborescent copolymers. Control over the branching density of G0PBG was investigated by varying the length and the deprotection level of the linear PBG substrates used in their synthesis. Three G0PBG cores with different branching densities, varying from a compact and dense to a loose and more porous structure, were thus synthesized. These amphiphilic copolymers behaved similar to unimolecular micelles in aqueous solutions, with a unimodal number- and volume-weighted size distributions in dynamic light scattering measurements. It was demonstrated that these biocompatible copolymers can encapsulate hydrophobic drugs such as doxorubicin (DOX) within their hydrophobic core with drug loading efficiencies of 42–65%. Sustained and pH-responsive DOX release was observed from the unimolecular micelles, which suggests that they could be useful as drug nanocarriers for cancer therapy. Full article

The major challenges of non-viral carriers are low transfection efficiency and high toxicity. To overcome this bottleneck, it is very important to investigate the structure-property-function (transfection efficiency) relationships of polycations. Herein, different length hydrophobic poly(l-leucine) chains in amphiphilic polypeptides were precisely synthesized by α-amino acid N-carboxyanhydrides (NCA) ring-opening polymerization and these biocompatible polypeptides were chosen as a model to further examine the transfection in vitro. These polypeptides were characterized by nuclear magnetic resonance spectroscopy (NMR) and size exclusion chromatography (SEC). Agarose gel electrophoresis (AGE) was employed to validate the ability of DNA condensation and transmission electron microscopy (TEM) was used to observe the assemblies of polyplexes. Cytotoxicity was evaluated in COS-7 cell lines and transfection was performed in normal cell COS-7 and cancer cell Hep G2. The results showed that NCA monomers were prepared and the amphiphilic polypeptides, poly(lysine(CBZ))₅₀-block-poly(l-leucine)₁₀, poly(l-lysine(CBZ))₅₀-block-poly(l-leucine)₁₅, and poly(l-lysine(CBZ))₅₀-block-poly(l-leucine)₂₅, were successfully synthesized with controlled molecular weight and narrow distribution. After deprotection of CBZ, these materials can condense plasmid DNA into 100 nm nanoparticles and the cellular uptake of polyplexes was as fast as 30 min. The transfection data shown these materials had a good transfection efficiency comparing to polyethylenimine (Branched, 25 kDa) while they displayed ignored cytotoxicity. More importantly, we discovered the length of hydrophobic poly(l-leucine) in amphiphilic polypeptides steadily regulates gene delivery efficiency in two kinds of cells ranking poly(l-lysine)₅₀-block-poly(l-leucine)₂₅ > poly(l-lysine)₅₀-block-poly(l-leucine)₁₅ > poly(l-lysine)₅₀-block-poly(l-leucine)₁₀. Full article

In this review, we provide a general and clear overview about the different alternatives reported to fabricate a myriad of polypeptide architectures based on the ring-opening polymerization of N-carbonyanhydrides (ROP NCAs). First of all, the strategies for the preparation of NCA monomers directly from natural occurring or from modified amino acids are analyzed. The synthetic alternatives to prepare non-functionalized and functionalized NCAs are presented. Protection/deprotection protocols, as well as other functionalization chemistries are discussed in this section. Later on, the mechanisms involved in the ROP NCA polymerization, as well as the strategies developed to reduce the eventually occurring side reactions are presented. Finally, a general overview of the synthetic strategies described in the literature to fabricate different polypeptide architectures is provided. This part of the review is organized depending on the complexity of the macromolecular topology prepared. Therefore, linear homopolypeptides, random and block copolypeptides are described first. The next sections include cyclic and branched polymers such as star polypeptides, polymer brushes and highly branched structures including arborescent or dendrigraft structures. Full article